Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count ≥ 100 x 109/L

G. V. Dahl, G. K. Rivera, A. T. Look, H. O. Hustu, D. K. Kalwinsky, Minnie Abromowitch, J. Mirro, J. Ochs, S. B. Murphy, R. K. Dodge, Pui Ching-Hon Pui

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Abstract

Childhood acute lymphoblastic leukemia with a initial leukocyte count ≥ 100 x 109/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 x 109/L was 44%, compared with 10% for matched controls (P < .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.

Original languageEnglish (US)
Pages (from-to)1015-1021
Number of pages7
JournalJournal of Clinical Oncology
Volume5
Issue number7
DOIs
StatePublished - Jan 1 1987

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Teniposide
Cytarabine
Leukocyte Count
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Remission Induction
Methotrexate
Drug Therapy
Cranial Irradiation
Asparaginase
Spinal Injections
6-Mercaptopurine
Hyperkalemia
Vincristine
Prednisone
Leukemia
Therapeutics
Survival Rate
Bone Marrow
Infection

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count ≥ 100 x 109/L. / Dahl, G. V.; Rivera, G. K.; Look, A. T.; Hustu, H. O.; Kalwinsky, D. K.; Abromowitch, Minnie; Mirro, J.; Ochs, J.; Murphy, S. B.; Dodge, R. K.; Ching-Hon Pui, Pui.

In: Journal of Clinical Oncology, Vol. 5, No. 7, 01.01.1987, p. 1015-1021.

Research output: Contribution to journalArticle

Dahl, GV, Rivera, GK, Look, AT, Hustu, HO, Kalwinsky, DK, Abromowitch, M, Mirro, J, Ochs, J, Murphy, SB, Dodge, RK & Ching-Hon Pui, P 1987, 'Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count ≥ 100 x 109/L', Journal of Clinical Oncology, vol. 5, no. 7, pp. 1015-1021. https://doi.org/10.1200/JCO.1987.5.7.1015
Dahl, G. V. ; Rivera, G. K. ; Look, A. T. ; Hustu, H. O. ; Kalwinsky, D. K. ; Abromowitch, Minnie ; Mirro, J. ; Ochs, J. ; Murphy, S. B. ; Dodge, R. K. ; Ching-Hon Pui, Pui. / Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count ≥ 100 x 109/L. In: Journal of Clinical Oncology. 1987 ; Vol. 5, No. 7. pp. 1015-1021.
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abstract = "Childhood acute lymphoblastic leukemia with a initial leukocyte count ≥ 100 x 109/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 x 109/L was 44{\%}, compared with 10{\%} for matched controls (P < .001). Remission induction rates in the two groups were similar (82{\%} v 72{\%}, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.",
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AU - Dahl, G. V.

AU - Rivera, G. K.

AU - Look, A. T.

AU - Hustu, H. O.

AU - Kalwinsky, D. K.

AU - Abromowitch, Minnie

AU - Mirro, J.

AU - Ochs, J.

AU - Murphy, S. B.

AU - Dodge, R. K.

AU - Ching-Hon Pui, Pui

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N2 - Childhood acute lymphoblastic leukemia with a initial leukocyte count ≥ 100 x 109/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 x 109/L was 44%, compared with 10% for matched controls (P < .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.

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